Genetic Variant EAF1:p.Asp206Asp (chr3-15436433-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_033083.7(EAF1):c.618C>T(p.Asp206Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,952 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 13 hom. )

Consequence

EAF1
NM_033083.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.40

Publications

2 publications found

Variant links:

Genes affected

EAF1 (HGNC:20907): (ELL associated factor 1) Enables transcription elongation regulator activity. Involved in regulation of transcription elongation from RNA polymerase II promoter. Located in intercellular bridge and nuclear body. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

EAF1 links:

METTL6 (HGNC:28343): (methyltransferase 6, tRNA N3-cytidine) Enables enzyme binding activity. Involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

METTL6 links:

EAF1-AS1 (HGNC:42328): (EAF1 antisense RNA 1)

EAF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 3-15436433-C-T is Benign according to our data. Variant chr3-15436433-C-T is described in ClinVar as Benign. ClinVar VariationId is 767886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.4 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00567 (864/152262) while in subpopulation AFR AF = 0.0186 (771/41534). AF 95% confidence interval is 0.0175. There are 7 homozygotes in GnomAd4. There are 413 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033083.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EAF1	NM_033083.7	MANE Select	c.618C>T	p.Asp206Asp	synonymous	Exon 5 of 6	NP_149074.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EAF1	ENST00000396842.7	TSL:1 MANE Select	c.618C>T	p.Asp206Asp	synonymous	Exon 5 of 6	ENSP00000380054.2	Q96JC9-1
METTL6	ENST00000598878.1	TSL:5	c.-125+2745G>A		intron	N/A	ENSP00000471485.1	M0R0W0
EAF1	ENST00000449565.1	TSL:2	n.*277C>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000399636.1	F8WFA5

Frequencies

GnomAD3 genomes

AF:

0.00567

AC:

862

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00956

GnomAD2 exomes

AF:

0.00161

AC:

405

AN:

251084

AF XY:

0.00117

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000737

AC:

1077

AN:

1461690

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

488

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.0176

AC:

588

AN:

33478

American (AMR)

AF:

0.00195

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000247

AC:

275

AN:

1111850

Other (OTH)

AF:

0.00162

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00567

AC:

864

AN:

152262

Hom.:

Cov.:

AF XY:

0.00555

AC XY:

413

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0186

AC:

771

AN:

41534

American (AMR)

AF:

0.00294

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68024

Other (OTH)

AF:

0.00946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00283

Hom.:

Bravo

AF:

0.00646

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

7.2

(source)

DANN

Benign

0.79

PhyloP100

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over